T Loftsson

..This short review is intended to provide both some basic science information as well as data on the ability to develop drugs in cyclodextrin-containing formulations...

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..When dissolved the energy of the system was lowered by expelling the drug molecules from the cyclodextrin cavities resulting in formation of supersaturated drug solutions and ultimately precipitation of the drug...

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..Decreased MIC could only be obtained by increasing the degradation half-life of the agents...

..Optimization of the soft antibacterial agents through SI optimization resulted in potent but chemically unstable quaternary ammonium antibacterial agents...

..Currently there are approximately 30 different pharmaceutical products worldwide containing drug/cyclodextrin complexes on the market...

..Thus, excess cyclodextrin, more than is needed to solubilize the drug in the aqueous exterior, will hamper drug delivery through biological membranes...

..Drug permeation patterns from cyclodextrin containing formulations through the membrane were similar to those previously observed for biological membranes such as hairless mouse skin and the eye cornea...

..New cyclodextrin-based technologies are constantly being developed and, thus, 100 years after their discovery cyclodextrins are still regarded as novel excipients of unexplored potential...

..The aqueous dexamethasone/gammaCD eye drop formulation was chemically stable during 7 months storage and well tolerated with no visible short-term side effects...

..This information can be useful not only in understanding the actions of cyclodextrin but also in expanding their application and uses...

..This latter property is examined herein as a function of the published literature as well as work completed in our laboratories...

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..This study aimed to develop low-viscosity aqueous eyedrops containing enalaprilat and its prodrug enalapril maleate in solution, and to evaluate the eyedrops in rabbits...

..Novel methods for solubility determinations, which can distinguish between individual solute molecules and small molecular aggregates, can possible improve the efficacy of HTS for new drug candidates...

..All these observations can be explained by formation of drug/cyclodextrin complex aggregates...

..Furthermore, the results indicate that drug/cyclodextrin complexes can self-associate to form water-soluble aggregates, which then can further solubilize the drug through non-inclusion complexation...

..Midazolam was absorbed rapidly reaching maximum serum concentrations of 54.3+/-5.0 ng/ml at 15+/-2 min. The elimination half-life of midazolam was 2.2+/-0.3 h and the absolute availability was 73+/-7%. All mean values+/-SEM...

..It was shown that the observed flux pattern was consistent with self-association of cyclodextrin complexes in the aqueous donor phase...

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..Thus, drug delivery from aqueous cyclodextrin solutions is both diffusion controlled and membrane controlled. It appears that cyclodextrins can only enhance topical drug delivery in the presence of water...

..However, although the soft analogs have been shown to possess antibacterial activity in in vitro studies, it is likely that their in vivo activity will be hampered by their chemical instability...

..The potassium halides had either increasing or decreasing effect on their aqueous solubility but did not have any effect on their permeability through UWL...

..The nasal formulation approaches the intravenous form in speed of absorption, serum concentration and clinical sedation effect. No serious side effects were observed...

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..Also, it was possible to increase the IOP-lowering effect of acetazolamide by formulating the drug as a suspension in an aqueous HP-beta-CyD vehicle...

..This aggregate formation was affected by the excipients and did influence drug availability from the formulations...

..The aggregate diameter was between 10 and 100 nm but larger aggregates with diameter of about 200 nm were formed through assemble of smaller aggregates...

..The drug release rate from the microcapsules could be controlled by addition of a plasticizer and it was sustained over extended time. Addition of solubilizing compounds to the dissolution medium did not affect the drug release rate...

..The metronidazole delivery through the skin was significant when the metronidazole oleate was used. This compound could therefore be considered as a suitable pro drug for dermal applications...

..The increasing realization that water influences the actions and interactions drugs and excipients opens a variety of new avenues with regard to the rationale design of useful dosage forms...

..In this study the effects of methazolamide are compared with those of dorzolamide (Trusopt)...

..CE is calculated from the slope of the phase-solubility diagrams, it is independent of both S0 and Sint, and more reliable when the influences of different pharmaceutical excipients on the solubilization are being investigated...

..Mixing alphaCD or betaCD with their more water-soluble derivatives only resulted in additive effects. Mixing gammaCD with HPgammaCD resulted in synergistic effect...

..They will facilitate eye drop formulations for drugs that otherwise might not be available for topical use, while improving absorption and stability and decreasing local irritation...

..Weakly protein bound drugs and drugs with low affinity towards HP?CD are insensitive to the cyclodextrin presence regardless their lipophilic properties...

..This predicts that diffusion fluxes should be lower in vitreous humour than in saline solution with lower viscosity. We test this hypothesis, which has implications for vitrectomy...

..However, most of the currently used membranes do not mimic mucosal membranes well, especially the aqueous mucous layer of the membranes. In this study we evaluated catfish (Anarichas lupus L) skin as a model membrane...

..Thus, this method would be suitable for screening of new drug candidates...

..Unionized amino- and carboxyl groups on polymers were found to be important structural feature of polymer for the formation of weak chemical bonds to mucus glycoproteins...

..In this article formation of CD aggregates and CD nanoparticles is reviewed with emphasis on the physicochemical properties of self-assembled CDs and CD complexes...

..However, when the results are interpreted it must be taken into account that the solvent medium can affect the chemical shifts of the fluorine peaks...

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..The 4,5-dihydroisoxazol-3-yl fatty acid esters of cycloserine can therefore be considered as new topical prodrugs with the potential use in treatment of various skin infections...

..4% (w/v). Lysine, polyvinylpyrrolidone and magnesium ions formed non-inclusion complexes resulting in formation of multiple-component cyclodextrin complexes in aqueous solutions with triclocarban...

..The cavity size and the charge and bulkiness of the cyclodextrin side-chains influenced the stability constant for complexation and the degradation rate of the curcumin molecule...

..The results obtained suggest that coevaporation and lyophilization methods yield a higher degree of amorphous entities and indicated formation of VP-SBEbetaCD binary and ternary complexes...

..This review is intended to give a general background to the use of cyclodextrin as solubilizers as well as highlight kinetic and thermodynamic tools and parameters useful in the study of drug solubilization by cyclodextrins...

..To compare 0.7% dexamethasone-cyclodextrin aqueous eye drop solution applied once daily with 0.1% dexamethasone sodium phosphate eye drops applied three times a day for the control of postoperative inflammation after cataract surgery...

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..This suggests that hydrophilic cyclodextrins enhance flux when the UWL resistance significantly contributes to the overall barrier resistance...

..0 w/w% and furthermore, a close relationship existed between the highly stabilizing effect and the degree of substitution of polar substituents...

..These data suggest that hydrophilic cyclodextrins might be useful formulation adjuncts in supersaturating drug delivery systems...

..We cannot disregard that only the traditional spray caused less sedation than intravenous administration. This finding needs to be confirmed in trials designed for this purpose...